Medullary thyroid carcinomas in transgenic mice expressing a Polyoma carboxyl-terminal truncated middle-T and wild type small-T antigens

A. Felici, M. Giorgio, N. Krauzewicz, C. Della Rocca, M. Santoro, P. Rovere, I. Manni, P. Amati, L. Pozzi

Research output: Contribution to journalArticle

Abstract

Medullary thyroid carcinoma (MTC) is a rare human tumor affecting the calcitonin-secreting c-cells of the thyroid. Here we report that two independent strains of transgenic mice expressing a Polyomavirus (Py) truncated middle-T antigen (ΔMT), consisting of the aminoterminal 304 amino acids, and the full length Py small-T antigen, developed multifocal bilateral MTCs with 100% penetrance. Occasionally one strain also developed mammary and bone tumors. Furthermore, offspring from both transgenic lines displayed pronounced waviness of the whiskers and fur, previously associated with defective epidermal growth factor receptor signaling. Transgene transcription, driven by the homologous early promoter/ enhancer, and the corresponding translation products were detected in tumors and in many other organs which did not develop pathologies. The subcellular distribution of ΔMT and its interactions with the adapter proteins of the SHC family have also been analysed. Our study describes a novel murine model of MTC and provides evidence that the N-terminal 304 amino acid fragment of Py middle-T antigen, possibly in co-operation with small-T antigen, acts as a potent oncogene in c-cells of the thyroid.

Original languageEnglish
Pages (from-to)2387-2395
Number of pages9
JournalOncogene
Volume18
Issue number14
Publication statusPublished - Apr 8 1999

Keywords

  • Medullary thyroid carcinoma
  • Middle-T
  • Oncogene
  • Transgenic

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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    Felici, A., Giorgio, M., Krauzewicz, N., Rocca, C. D., Santoro, M., Rovere, P., Manni, I., Amati, P., & Pozzi, L. (1999). Medullary thyroid carcinomas in transgenic mice expressing a Polyoma carboxyl-terminal truncated middle-T and wild type small-T antigens. Oncogene, 18(14), 2387-2395.